Chronic pain is an enormous problem in the United States: it is estimated that 30 to 100 million people suffer from it. Often, current treatments are ineffective and the population of sufferers is often described as "under-served." According to recent data, chronic pain is transmitted through the Substance P receptor-expressing neurons of the dorsal horn of the spinal cord. Elimination of these neurons terminates transmission of the chronic pain signal in several rat models. However, this method relied on the death of spinal cord neurons. An alternative method that would maintain the integrity of the neuronal system would be to only disrupt the activities of these neurons. This could be achieved by internalizing molecules into Substance P receptor-expressing neurons that interfere with the ability to transmit the chronic pain signal. It is proposed in this Phase I application to demonstrate that an expression system, useful for expressing molecules that can cause this disruption, can be internalized into Substance P receptor-expressing neurons and can express a marker protein, green fluorescent protein. The success of this application could result in the resolution of serious problems that interfere with the treatment of chronic pain. PROPOSED COMMERCIAL APPLICATION: This proposal will result in the development of an expression system for use in internally manipulating cells to disrupt or alter their function. Such a system would have many applications in scientific research, not only in chronic pain, but in any area where scientists seek to alter cell processes. Additionally, an expression system that can diminish rather than destroy a cell's function would have great possibility in the treatment of disease.